Sorry your sleep is so messed-up. I note that you say you've been taking "8 mg at bedtime (whenever that is)." A couple of things on that. As George N and Kitano have alluded, you may be encountering a paradoxical response to so high a dose. This isn't an ε4 thing (or, there is no research to suggest that): 0.3 mg (300 mcg) is sufficient to raise levels to normal physiological youthful ones (and actually, to supraphysiologic
levels in older people(6)) and apparently works as well as higher doses ((1,2,4,5), and see (3)). Doses of 3 mg (and up) produce an excessive fall in body temperature and 'hangover' sleepiness.(4) I know that the most common dose in health food stores is 10 mg; this is thanks to the unfortunate recommendation of the once-notorious Melatonin Miracle
, which was extrapolating from poorly-done rodent life extension studies.(7)
I will also note that one clinical trial found 2 mg of controlled-release M to improve not only sleep, but cognitive function and instrumental activities of daily living in people with mild-to-moderate AD (genotype undetermined). Whether this is just the effect of ameliorating the normal deleterious effects of sleep deprivation, or also had some effect on the disease itself, is unknown, and thus whether there's a rationale (beyond silly "it's an antioxidant!" arguments) for taking it preventively.
Also, you say you've been taking "8 mg at bedtime (whenever that is
)." As you may know, the reason why M promotes sleep is that it's an endocrine regulator of circadian rhythms: it sends out the message from the central body clock that it's bed-time now and everyone should wrap up their daytime business. This is why it's particularly useful for jet lag per se. If you're taking an agent that entrains your circadian rhythm at different times
night after night, I expect
that you're going to bugger yourself up even worse over time. Additionally, a regular bedtime is a core element of "sleep hygiene
," so if you're having trouble sleeping you should really be endeavoring to make this time as consistent as you can, M or no.
Also, you mention caffeine ... it's important to avoid C for at least 6 hours before bedtime. I know this may sound like a lot, and the U of M site I just linked indicates 4-6 h rather than 6, but a recent study finds that 400 mg of C interferes with proper sleep cycling for at least 6 h, even though the subjects did not subjectively notice any effect:
Caffeine-induced sleep disturbance was detected by both the self-report diary and objective sleep measures when taken at bedtime and 3 hours prior to bedtime, whereas only the objective measure detected differences when caffeine was taken 6 hours prior to bedtime.(9)
This would mean that you're not getting the full cognitive or tissue-repair benefits of what sleep you get, even if you're ostensibly asleep for the same amount of time. And they didn't test a window longer than 6 h, so it's at least possible that the effect is present even longer than that; indeed, you'd actually expect it to, particularly at higher dose, since 6 h is the average half-life
400 mg is the amount present in 1-4 cups of brewed coffee, depending on bean variability and strength and method of brew: an 8 oz cup of home-brew tends to contain ~100 mg, but (a) 12 oz is the least that almost anyone drinks at a time any more, and (b) tyical Starbucks and pressed coffees contain 400 mg. If you're actually having trouble even getting to or staying "asleep," I'd really urge you to wean yourself off of the afternoon caffeine habit.
(On the other hand, I'd encourage you not to go off C altogether: there's experimental and epidemiological evidence suggesting that moderate-to-high coffee consumption may reduce your risk of Alzheimer's
, though the data are not strong and the epidemiology is quite inconsistent).
Hope that's useful. Sleep well soon!References
1: Zhdanova IV, Wurtman RJ, Morabito C, Piotrovska VR, Lynch HJ. Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans. Sleep. 1996 Jun;19(5):423-31. PubMed PMID: 8843534.
2: Zhdanova IV, Wurtman RJ, Lynch HJ, Ives JR, Dollins AB, Morabito C, Matheson JK, Schomer DL. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther. 1995 May;57(5):552-8. PubMed PMID: 7768078.
3: Brzezinski A, Vangel MG, Wurtman RJ, Norrie G, Zhdanova I, Ben-Shushan A, Ford
I. Effects of exogenous melatonin on sleep: a meta-analysis
. Sleep Med Rev. 2005 Feb;9(1):41-50. PubMed PMID: 15649737.
4: Zhdanova IV, Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab. 2001 Oct;86(10):4727-30. PubMed PMID: 11600532.
5: Dollins AB, Zhdanova IV, Wurtman RJ, Lynch HJ, Deng MH. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1824-8. PubMed PMID: 8127888; PubMed Central PMCID: PMC43256.
6: Zhdanova IV, Wurtman RJ, Balcioglu A, Kartashov AI, Lynch HJ. Endogenous melatonin levels and the fate of exogenous melatonin: age effects. J Gerontol A Biol Sci Med Sci. 1998 Jul;53(4):B293-8. PubMed PMID: 18314560.
7: Pierpaoli W, Dall'Ara A, Pedrinis E, Regelson W. The pineal control of aging. The effects of melatonin and pineal grafting on the survival of older mice
. Ann N Y Acad Sci. 1991;621:291-313. PMID: 1859093 [PubMed - indexed for MEDLINE]
8: Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, Frydman-Marom A, Zisapel N. Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer's disease: a 6-month, randomized, placebo-controlled, multicenter trial.
Clin Interv Aging. 2014 Jun 18;9:947-61. doi: 10.2147/CIA.S65625. eCollection 2014. PubMed PMID: 24971004; PubMed Central PMCID: PMC4069047.
9: Drake C, Roehrs T, Shambroom J, Roth T. Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed
. J Clin Sleep Med. 2013 Nov 15;9(11):1195-200. doi: 10.5664/jcsm.3170. PubMed PMID: 24235903; PubMed Central PMCID: PMC3805807.